Development of New Vaccines and Drugs For TB: Limitations and Potential Strategic Errors

Bibliography

• Glaziou P , FloydK, RaviglioneM: Global burden and epidemiology of tuberculosis.Clin. Chest Med.30 , 621–636 (2009).
   PubMed Web of Science ®Google Scholar
• Bifani PJ , MathemaB, KurepinaNE, KreiswirthBN: Global dissemination of the Mycobacterium tuberculosis W-Beijing family strains.Trends Microbiol.10 , 45–52 (2002).
   PubMed Web of Science ®Google Scholar
• Wright A , ZignolM, VanDeun Aet al.: Epidemiology of antituberculosis drug resistance 2002–2007: an updated analysis of the Global Project on Anti-Tuberculosis Drug Resistance Surveillance.Lancet373(9678) , 1861–1873 (2009).
   PubMed Web of Science ®Google Scholar
• Velayati AA , MasjediMR, FarniaPet al. : Emergence of new forms of totally drug-resistant tuberculosis bacilli: super extensively drug-resistant tuberculosis or totally drug-resistant strains in Iran.Chest136 , 420–425 (2009).
   PubMed Web of Science ®Google Scholar
• Dye C : Doomsday postponed? Preventing and reversing epidemics of drug-resistant tuberculosis.Nat. Rev. Microbiol.7 , 81–87 (2009).
   PubMed Web of Science ®Google Scholar
• Dye C , EspinalMA: Will tuberculosis become resistant to all antibiotics?Proc. Biol. Sci.268 , 45–52 (2001).
   PubMed Web of Science ®Google Scholar
• Fauci AS : Multidrug-resistant and extensively drug-resistant tuberculosis: the National Institute of Allergy and Infectious Diseases Research agenda and recommendations for priority research.J. Infect. Dis.197 , 1493–1498 (2008).
   PubMed Web of Science ®Google Scholar
• Wells CD , CegielskiJP, NelsonLJet al. : HIV infection and multidrug-resistant tuberculosis: the perfect storm.J. Infect. Dis.196(Suppl. 1) , S86–S107 (2007).
   PubMed Web of Science ®Google Scholar
• Nunn P , ReidA, DeCock KM: Tuberculosis and HIV infection: the global setting.J. Infect. Dis.196(Suppl. 1) , S5–S14 (2007).
   PubMed Web of Science ®Google Scholar
• Day JH , GrantAD, FieldingKLet al. : Does tuberculosis increase HIV load?J. Infect. Dis.190 , 1677–1684 (2004).
   PubMed Web of Science ®Google Scholar
• Whalen C , HorsburghCR, HomD, LahartC, SimberkoffM, EllnerJ: Accelerated course of human immunodeficiency virus infection after tuberculosis.Am. J. Respir. Crit. Care Med.151 , 129–135 (1995).
   PubMed Web of Science ®Google Scholar
• Rajbhandary SS , MarksSM, BockNN: Costs of patients hospitalized for multidrug-resistant tuberculosis.Int. J. Tuberc. Lung Dis.8 , 1012–1016 (2004).
   PubMed Web of Science ®Google Scholar
• White VL , Moore-GillonJ: Resource implications of patients with multidrug resistant tuberculosis.Thorax55 , 962–963 (2000).
   PubMed Web of Science ®Google Scholar
• Bock NN , JensenPA, MillerB, NardellE: Tuberculosis infection control in resource-limited settings in the era of expanding HIV care and treatment.J. Infect. Dis.196(Suppl.1) , S108–S113 (2007).
   PubMed Web of Science ®Google Scholar
• Quy HT , BuuTN, CobelensFG, LanNT, LambregtsCS, BorgdorffMW: Drug resistance among smear-positive tuberculosis patients in Ho Chi Minh City, Vietnam.Int. J. Tuberc. Lung Dis.10 , 160–166 (2006).
   PubMed Web of Science ®Google Scholar
• Dye C , LonnrothK, JaramilloE, WilliamsBG, RaviglioneM: Trends in tuberculosis incidence and their determinants in 134 countries.Bull. World Health Organ.87 , 683–691 (2009).
   PubMed Web of Science ®Google Scholar
• Gandhi NR , MollA, SturmAWet al. : Extensively drug-resistant tuberculosis as a cause of death in patients co-infected with tuberculosis and HIV in a rural area of South Africa.Lancet368 , 1575–1580 (2006).
   PubMed Web of Science ®Google Scholar
• Migliori GB , SotgiuG: XDR tuberculosis in South Africa: old questions, new answers.Lancet375 , 1760–1761 (2010).
   PubMed Web of Science ®Google Scholar
• Kliiman K , AltrajaA: Predictors of extensively drug-resistant pulmonary tuberculosis.Ann. Intern. Med.150 , 766–775 (2009).
   PubMed Web of Science ®Google Scholar
• Cooper AM : Cell-mediated immune responses in tuberculosis.Annu. Rev. Immunol.27 , 393–422 (2009).
   PubMed Web of Science ®Google Scholar
• North RJ : T cell dependence of macrophage activation and mobilization during infection with Mycobacterium tuberculosis.Infect. Immun.10 , 66–71 (1974).
   PubMed Web of Science ®Google Scholar
• Johnson CM , CooperAM, FrankAA, OrmeIM: Adequate expression of protective immunity in the absence of granuloma formation in Mycobacterium tuberculosis-infected mice with a disruption in the intracellular adhesion molecule 1 gene.Infect. Immun.66 , 1666–1670 (1998).
   PubMed Web of Science ®Google Scholar
• Orme IM , CollinsFM: Protection against Mycobacterium tuberculosis infection by adoptive immunotherapy. Requirement for T cell-deficient recipients.J. Exp. Med.158 , 74–83 (1983).
   PubMed Web of Science ®Google Scholar
• Orme IM : The kinetics of emergence and loss of mediator T lymphocytes acquired in response to infection with Mycobacterium tuberculosis.J. Immunol.138 , 293–298 (1987).
   PubMed Web of Science ®Google Scholar
• Junqueira-Kipnis AP , KipnisA, JamiesonAet al. : NK cells respond to pulmonary infection with Mycobacterium tuberculosis, but play a minimal role in protection.J. Immunol.171 , 6039–6045 (2003).
   PubMed Web of Science ®Google Scholar
• Lockhart E , GreenAM, FlynnJL: IL-17 production is dominated by γδ T cells rather than CD4 T cells during Mycobacterium tuberculosis infection.J. Immunol.177 , 4662–4669 (2006).
   PubMed Web of Science ®Google Scholar
• D‘Souza CD , CooperAM, FrankAA, MazzaccaroRJ, BloomBR, OrmeIM: An anti-inflammatory role for γ δ T lymphocytes in acquired immunity to Mycobacterium tuberculosis.J. Immunol.158 , 1217–1221 (1997).
   PubMed Web of Science ®Google Scholar
• Khader SA , CooperAM: IL-23 and IL-17 in tuberculosis.Cytokine41 , 79–83 (2008).
   PubMed Web of Science ®Google Scholar
• Ordway D , Henao-TamayoM, HartonMet al. : The hypervirulent Mycobacterium tuberculosis strain HN878 induces a potent Th1 response followed by rapid down-regulation.J. Immunol.179 , 522–531 (2007).
   PubMed Web of Science ®Google Scholar
• Einarsdottir T , LockhartE, FlynnJL: Cytotoxicity and secretion of γ interferon are carried out by distinct CD8 T cells during Mycobacterium tuberculosis infection.Infect. Immun.77 , 4621–4630 (2009).
   PubMed Web of Science ®Google Scholar
• Flynn JL , GoldsteinMM, TrieboldKJ, KollerB, BloomBR: Major histocompatibility complex class I-restricted T cells are required for resistance to Mycobacterium tuberculosis infection.Proc. Natl Acad. Sci. USA89 , 12013–12017 (1992).
   PubMed Web of Science ®Google Scholar
• Wu Y , WoodworthJS, ShinDS, MorrisS, BeharSM: Vaccine-elicited 10-kilodalton culture filtrate protein-specific CD8+ T cells are sufficient to mediate protection against Mycobacterium tuberculosis infection.Infect. Immun.76 , 2249–2255 (2008).
   PubMed Web of Science ®Google Scholar
• Turner J , D‘SouzaCD, PearlJEet al. : CD8- and CD95/95L-dependent mechanisms of resistance in mice with chronic pulmonary tuberculosis.Am. J. Respir. Cell. Mol. Biol.24 , 203–209 (2001).
   PubMed Web of Science ®Google Scholar
• Gonzalez-Juarrero M , TurnerOC, TurnerJ, MariettaP, BrooksJV, OrmeIM: Temporal and spatial arrangement of lymphocytes within lung granulomas induced by aerosol infection with Mycobacterium tuberculosis.Infect. Immun.69 , 1722–1728 (2001).
   PubMed Web of Science ®Google Scholar
• Orme I , Gonzalez-JuarreroM: Animal models of M. tuberculosis infection.Curr. Protoc. Microbiol. Chapter 10, Unit 10A.5 (2007).
   PubMedGoogle Scholar
• Young D : Animal models of tuberculosis.Eur.J. Immunol.39 , 2011–2014 (2009).
   PubMed Web of Science ®Google Scholar
• Flynn JL , ChanJ: Immunology of tuberculosis.Annu. Rev. Immunol.19 , 93–129 (2001).
   PubMed Web of Science ®Google Scholar
• Orme IM : Preclinical testing of new vaccines for tuberculosis: a comprehensive review.Vaccine24 , 2–19 (2006).
   PubMed Web of Science ®Google Scholar
• Kondratieva EV , EvstifeevVV, KondratievaTKet al. : I/St mice hypersusceptible to Mycobacterium tuberculosis are resistant to M. avium.Infect. Immun.75 , 4762–4768 (2007).
   PubMed Web of Science ®Google Scholar
• Pichugin AV , YanBS, SloutskyA, KobzikL, KramnikI: Dominant role of the sst1 locus in pathogenesis of necrotizing lung granulomas during chronic tuberculosis infection and reactivation in genetically resistant hosts.Am. J. Pathol.174 , 2190–2201 (2009).
   PubMed Web of Science ®Google Scholar
• Sugawara I , UdagawaT, YamadaH: Rat neutrophils prevent the development of tuberculosis.Infect. Immun.72 , 1804–1806 (2004).
   PubMed Web of Science ®Google Scholar
• Sugawara I , YamadaH, MizunoS: Nude rat (F344/N-rnu) tuberculosis.Cell Microbiol.8 , 661–667 (2006).
   PubMed Web of Science ®Google Scholar
• Tsenova L , EllisonE, HarbacheuskiRet al. : Virulence of selected Mycobacterium tuberculosis clinical isolates in the rabbit model of meningitis is dependent on phenolic glycolipid produced by the bacilli.J. Infect. Dis.192 , 98–106 (2005).
   PubMed Web of Science ®Google Scholar
• Manabe YC , DannenbergAMJr, TyagiSKet al.: Different strains of Mycobacterium tuberculosis cause various spectrums of disease in the rabbit model of tuberculosis.Infect. Immun.71 , 6004–6011 (2003).
   PubMed Web of Science ®Google Scholar
• Buddle BM , SkinnerMA, WedlockDN, deLisle GW, VordermeierHM, HewinsonRG: Cattle as a model for development of vaccines against human tuberculosis.Tuberculosis (Edinb.)85 , 19–24 (2005).
   PubMed Web of Science ®Google Scholar
• Orme IM : Immunology and vaccinology of tuberculosis: can lessons from the mouse be applied to the cow?Tuberculosis (Edinb.)81 , 109–113 (2001).
   PubMed Web of Science ®Google Scholar
• Basaraba RJ : Experimental tuberculosis: the role of comparative pathology in the discovery of improved tuberculosis treatment strategies.Tuberculosis (Edinb.)88(Suppl. 1) , S35–S47 (2008).
   PubMed Web of Science ®Google Scholar
• McMurray DN : Determinants of vaccine-induced resistance in animal models of pulmonary tuberculosis.Scand. J. Infect. Dis.33 , 175–178 (2001).
   PubMed Web of Science ®Google Scholar
• McMurray DN , CollinsFM, DannenbergAMJr, SmithDW: Pathogenesis of experimental tuberculosis in animal models.Curr. Top. Microbiol. Immunol.215 , 157–179 (1996).
   PubMed Web of Science ®Google Scholar
• Basaraba RJ , OrmeIM: Pulmonary tuberculosis in the guinea pig. In:A Color Atlas of Comparative Pathology of Pulmonary Tuberculosis. LeongFJ, DartoisV, DickT (Eds). CRC Press, LA, USA131–155 (2010).
   Google Scholar
• Ly LH , RussellMI, McMurrayDN: Cytokine profiles in primary and secondary pulmonary granulomas of Guinea pigs with tuberculosis.Am. J. Respir. Cell. Mol. Biol.38 , 455–462 (2008).
   PubMed Web of Science ®Google Scholar
• Ordway D , PalanisamyG, Henao-TamayoMet al. : The cellular immune response to Mycobacterium tuberculosis infection in the guinea pig.J. Immunol.179 , 2532–2541 (2007).
   PubMed Web of Science ®Google Scholar
• Turner OC , BasarabaRJ, FrankAA, OrmeIM: Granuloma formation in mouse and guinea pig models of experimental tuberculosis. In:Granulomatous Infections and Inflammation: Cellular and Molecular Mechanisms. BorosDL (Ed.). ASM Press, Washington, DC, USA65–84 (2003).
   Google Scholar
• Turner OC , BasarabaRJ, OrmeIM: Immunopathogenesis of pulmonary granulomas in the guinea pig after infection with Mycobacterium tuberculosis.Infect. Immun.71 , 864–871 (2003).
   PubMed Web of Science ®Google Scholar
• Williams A , HallY, OrmeIM: Evaluation of new vaccines for tuberculosis in the guinea pig model.Tuberculosis (Edinb.)89 , 389–397 (2009).
   PubMed Web of Science ®Google Scholar
• Ordway DJ , ShanleyCA, CarawayMLet al. : Evaluation of standard chemotherapy in the guinea pig model of tuberculosis.Antimicrob. Agents Chemother.54 , 1820–1833 (2010).
   PubMed Web of Science ®Google Scholar
• Capuano SV , CroixDA, PawarSet al. : Experimental Mycobacterium tuberculosis infection of cynomolgus macaques closely resembles the various manifestations of human M. tuberculosis infection.Infect. Immun.71 , 5831–5844 (2003).
   PubMed Web of Science ®Google Scholar
• Walsh GP , TanEV, dela Cruz ECet al.: The Philippine cynomolgus monkey (Macaca fasicularis) provides a new nonhuman primate model of tuberculosis that resembles human disease.Nat. Med.2 , 430–436 (1996).
   PubMed Web of Science ®Google Scholar
• Lin PL , RodgersM, SmithLet al. : Quantitative comparison of active and latent tuberculosis in the cynomolgus macaque model.Infect. Immun.77 , 4631–4642 (2009).
   PubMed Web of Science ®Google Scholar
• Langermans JA , DohertyTM, VervenneRAet al. : Protection of macaques against Mycobacterium tuberculosis infection by a subunit vaccine based on a fusion protein of antigen 85B and ESAT-6.Vaccine23 , 2740–2750 (2005).
   PubMed Web of Science ®Google Scholar
• Sharpe SA , McShaneH, DennisMJet al. : Establishment of an aerosol challenge model of tuberculosis in rhesus macaques and an evaluation of endpoints for vaccine testing.Clin. Vaccine Immunol.17 , 1170–1182 (2010).
   PubMed Web of Science ®Google Scholar
• Tobin DM , VaryJCJr, RayJPet al.: The lta4h locus modulates susceptibility to mycobacterial infection in zebrafish and humans.Cell140 , 717–730 (2010).
   PubMed Web of Science ®Google Scholar
• Rhoades ER , FrankAA, OrmeIM: Progression of chronic pulmonary tuberculosis in mice aerogenically infected with virulent Mycobacterium tuberculosis.Tuber. Lung Dis.78 , 57–66 (1997).
   PubMedGoogle Scholar
• Chackerian AA , AltJM, PereraTV, DascherCC, BeharSM: Dissemination of Mycobacterium tuberculosis is influenced by host factors and precedes the initiation of T-cell immunity.Infect. Immun.70 , 4501–4509 (2002).
   PubMed Web of Science ®Google Scholar
• Wolf AJ , DesvignesL, LinasBet al. : Initiation of the adaptive immune response to Mycobacterium tuberculosis depends on antigen production in the local lymph node, not the lungs.J. Exp. Med.205 , 105–115 (2008).
   PubMed Web of Science ®Google Scholar
• Pedrosa J , SaundersBM, AppelbergR, OrmeIM, SilvaMT, CooperAM: Neutrophils play a protective nonphagocytic role in systemic Mycobacterium tuberculosis infection of mice.Infect. Immun.68 , 577–583 (2000).
   PubMed Web of Science ®Google Scholar
• Dannenberg AM : Immunopathogenesis of pulmonary tuberculosis.Hosp. Pract.28 , 51–58 (1993).
   PubMed Web of Science ®Google Scholar
• Dannenberg AM : Roles of cytotoxic delayed-type hypersensitivity and macrophage-activating cell-mediated immunity in the pathogenesis of tuberculosis.Immunobiology191 , 461–473 (1994).
   PubMed Web of Science ®Google Scholar
• Russell DG , BarryCE, FlynnJL: Tuberculosis: what we don‘t know can, and does, hurt us.Science28 , 852–856 (2010).
   Google Scholar
• Basaraba RJ , SmithEE, ShanleyCA, OrmeIM: Pulmonary lymphatics are primary sites of Mycobacterium tuberculosis infection in guinea pigs infected by aerosol.Infect. Immun.74 , 5397–5401 (2006).
   PubMed Web of Science ®Google Scholar
• Lenaerts AJ , HoffD, AlySet al. : Location of persisting mycobacteria in a Guinea pig model of tuberculosis revealed by r207910.Antimicrob. Agents Chemother.51 , 3338–3345 (2007).
   PubMed Web of Science ®Google Scholar
• Ryan GJ , HoffDR, DriverERet al. : Multiple M. tuberculosis phenotypes in mouse and guinea pig lung tissue revealed by a dual-staining approach.PLoS ONE5 , E11108 (2010).
   PubMed Web of Science ®Google Scholar
• Via LE , LinPL, RaySMet al. : Tuberculous granulomas are hypoxic in guinea pigs, rabbits, and nonhuman primates.Infect. Immun.76 , 2333–2340 (2008).
   PubMed Web of Science ®Google Scholar
• Rustad TR , SherridAM, MinchKJ, ShermanDR: Hypoxia: a window into Mycobacterium tuberculosis latency.Cell Microbiol.11 , 1151–1159 (2009).
   PubMed Web of Science ®Google Scholar
• Dye C , WilliamsBG: The population dynamics and control of tuberculosis.Science328 , 856–861 (2010).
   PubMed Web of Science ®Google Scholar
• Lienhardt C , VernonA, RaviglioneMC: New drugs and new regimens for the treatment of tuberculosis: review of the drug development pipeline and implications for national programmes.Curr. Opin. Pulm. Med.16 , 186–193 (2010).
   PubMed Web of Science ®Google Scholar
• Kliiman K , AltrajaA: Predictors of poor treatment outcome in multi- and extensively drug-resistant pulmonary TB.Eur. Respir. J.33 , 1085–1094 (2009).
   PubMed Web of Science ®Google Scholar
• Mak A , ThomasA, DelGranado M, ZaleskisR, MouzafarovaN, MenziesD: Influence of multidrug resistance on tuberculosis treatment outcomes with standardized regimens.Am. J. Respir. Crit. Care Med.178 , 306–312 (2008).
   PubMed Web of Science ®Google Scholar
• Ginsberg AM , SpigelmanM: Challenges in tuberculosis drug research and development.Nat. Med.13 , 290–294 (2007).
   PubMed Web of Science ®Google Scholar
• Lenaerts AJ , DegrooteMA, OrmeIM: Preclinical testing of new drugs for tuberculosis: current challenges.Trends Microbiol.16 , 48–54 (2008).
   PubMed Web of Science ®Google Scholar
• Nuermberger EL , YoshimatsuT, TyagiSet al. : Moxifloxacin-containing regimen greatly reduces time to culture conversion in murine tuberculosis.Am. J. Respir. Crit. Care Med.169 , 421–426 (2004).
   PubMed Web of Science ®Google Scholar
• Dorman SE , JohnsonJL, GoldbergSet al. : Substitution of moxifloxacin for isoniazid during intensive phase treatment of pulmonary tuberculosis.Am. J. Respir. Crit. Care Med.180 , 273–280 (2009).
   PubMed Web of Science ®Google Scholar
• Brooks JV , FurneySK, OrmeIM: Metronidazole therapy in mice infected with tuberculosis.Antimicrob. Agents Chemother.43 , 1285–1288 (1999).
   PubMed Web of Science ®Google Scholar
• Dhillon J , AllenBW, HuYM, CoatesAR, MitchisonDA: Metronidazole has no antibacterial effect in Cornell model murine tuberculosis.Int. J. Tuberc. Lung Dis.2 , 736–742 (1998).
   PubMed Web of Science ®Google Scholar
• Hoff DR , CarawayML, BrooksEJet al. : Metronidazole lacks antibacterial activity in guinea pigs infected with Mycobacterium tuberculosis.Antimicrob. Agents Chemother.52 , 4137–4140 (2008).
   PubMed Web of Science ®Google Scholar
• Klinkenberg LG , SutherlandLA, BishaiWR, KarakousisPC: Metronidazole lacks activity against Mycobacterium tuberculosis in an in vivo hypoxic granuloma model of latency.J. Infect. Dis.198 , 275–283 (2008).
   PubMed Web of Science ®Google Scholar
• Dutt AK , SteadWW: Tuberculosis in the elderly.Med. Clin. North Am.77 , 1353–1368 (1993).
   PubMed Web of Science ®Google Scholar
• Barry CE 3rd , BoshoffHI, DartoisVet al.: The spectrum of latent tuberculosis: rethinking the biology and intervention strategies.Nat. Rev. Microbiol.7 , 845–855 (2009).
   PubMed Web of Science ®Google Scholar
• Tufariello JM , ChanJ, FlynnJL: Latent tuberculosis: mechanisms of host and bacillus that contribute to persistent infection.Lancet Infect. Dis.3 , 578–590 (2003).
   PubMed Web of Science ®Google Scholar
• Chiang CY , RileyLW: Exogenous reinfection in tuberculosis.Lancet Infect. Dis.5 , 629–636 (2005).
   PubMed Web of Science ®Google Scholar
• Orme IM : The latent tuberculosis bacillus (I‘ll let you know if I ever meet one).Int. J. Tuberc. Lung Dis.5 , 589–593 (2001).
   PubMed Web of Science ®Google Scholar
• Gomez JE , McKinneyJD: M. tuberculosis persistence, latency, and drug tolerance.Tuberculosis (Edinb.)84 , 29–44 (2004).
   PubMed Web of Science ®Google Scholar
• Manabe YC , BishaiWR: Latent Mycobacterium tuberculosis-persistence, patience, and winning by waiting.Nat. Med.6 , 1327–1329 (2000).
   PubMed Web of Science ®Google Scholar
• Smith DW , BalasubramanianV, WiegeshausE: A guinea pig model of experimental airborne tuberculosis for evaluation of the response to chemotherapy: the effect on bacilli in the initial phase of treatment.Tubercle72 , 223–231 (1991).
   PubMedGoogle Scholar
• Basaraba RJ , Bielefeldt-OhmannH, EschelbachEKet al. : Increased expression of host iron-binding proteins precedes iron accumulation and calcification of primary lung lesions in experimental tuberculosis in the guinea pig.Tuberculosis (Edinb.)88 , 69–79 (2008).
   PubMed Web of Science ®Google Scholar
• Ojha AK , BaughnAD, SambandanDet al. : Growth of Mycobacterium tuberculosis biofilms containing free mycolic acids and harbouring drug-tolerant bacteria.Mol. Microbiol.69 , 164–174 (2008).
   PubMed Web of Science ®Google Scholar
• Beresford B , SadoffJC: Update on research and development pipeline: tuberculosis vaccines.Clin. Infect. Dis.50(Suppl. 3) , S178–S183 (2010).
   PubMed Web of Science ®Google Scholar
• Andersen P : TB vaccines: progress and problems.Trends Immunol.22 , 160–168 (2001).
   PubMed Web of Science ®Google Scholar
• Kaufmann SH : Is the development of a new tuberculosis vaccine possible?Nat. Med.6 , 955–960 (2000).
   PubMed Web of Science ®Google Scholar
• Orme IM : The search for new vaccines against tuberculosis.J. Leukoc. Biol.70 , 1–10 (2001).
   PubMed Web of Science ®Google Scholar
• Orme IM , McMurrayDN, BelisleJT: Tuberculosis vaccine development: recent progress.Trends Microbiol.9 , 115–118 (2001).
   PubMed Web of Science ®Google Scholar
• Skeiky YA , SadoffJC: Advances in tuberculosis vaccine strategies.Nat. Rev. Microbiol.4 , 469–476 (2006).
   PubMed Web of Science ®Google Scholar
• Aagaard C , HoangTT, IzzoAet al. : Protection and polyfunctional T cells induced by Ag85B-TB10.4 /IC31 against Mycobacterium tuberculosis is highly dependent on the antigen dose.PLoS ONE4 , E5930 (2009).
   PubMed Web of Science ®Google Scholar
• Skeiky YA , AldersonMR, OvendalePJet al. : Differential immune responses and protective efficacy induced by components of a tuberculosis polyprotein vaccine, Mtb72F, delivered as naked DNA or recombinant protein.J. Immunol.172 , 7618–7628 (2004).
   PubMed Web of Science ®Google Scholar
• Brandt L , SkeikyYA, AldersonMRet al. : The protective effect of the Mycobacterium bovis BCG vaccine is increased by coadministration with the Mycobacterium tuberculosis 72-kilodalton fusion polyprotein Mtb72F in M. tuberculosis-infected guinea pigs.Infect. Immun.72 , 6622–6632 (2004).
   PubMed Web of Science ®Google Scholar
• Reed SG , ColerRN, DalemansWet al. : Defined tuberculosis vaccine, Mtb72F/AS02A, evidence of protection in cynomolgus monkeys.Proc. Natl Acad. Sci. USA106 , 2301–2306 (2009).
   PubMed Web of Science ®Google Scholar
• Baldwin SL , BertholetS, KahnMet al. : Intradermal immunization improves protective efficacy of a novel TB vaccine candidate.Vaccine27 , 3063–3071 (2009).
   PubMed Web of Science ®Google Scholar
• Bertholet S , IretonGC, KahnMet al. : Identification of human T cell antigens for the development of vaccines against Mycobacterium tuberculosis.J. Immunol.181 , 7948–7957 (2008).
   PubMed Web of Science ®Google Scholar
• Coler RN , DillonDC, SkeikyYAet al. : Identification of Mycobacterium tuberculosis vaccine candidates using human CD4+ T-cells expression cloning.Vaccine27 , 223–233 (2009).
   PubMed Web of Science ®Google Scholar
• Bertholet S , IretonGC, OrdwayDJet al. : A defined tuberculosis vaccine candidate boosts BCG and protects against multidrug resistant Mycobacterium tuberculosis.Sci. Transl. Med.2(53) , 53ra74 (2010).
   PubMed Web of Science ®Google Scholar
• Orme IM : Current progress in tuberculosis vaccine development.Vaccine23 , 2105–2108 (2005).
   PubMed Web of Science ®Google Scholar
• de Cassan SC , PathanAA, SanderCRet al. : Investigating the induction of vaccine-induced Th17 and regulatory T cells in healthy, Mycobacterium bovis BCG-immunized adults vaccinated with a new tuberculosis vaccine, MVA85A.Clin. Vaccine Immunol.17 , 1066–1073 (2010).
   PubMedGoogle Scholar
• Kolibab K , YangA, DerrickSC, WaldmannTA, PereraLP, MorrisSL: Highly persistent and effective prime/boost regimens against tuberculosis that use a multivalent modified vaccine virus Ankara-based tuberculosis vaccine with interleukin-15 as a molecular adjuvant.Clin. Vaccine Immunol.17 , 793–801 (2010).
   PubMed Web of Science ®Google Scholar
• Sun R , SkeikyYA, IzzoAet al. : Novel recombinant BCG expressing perfringolysin O and the over-expression of key immunodominant antigens; pre-clinical characterization, safety and protection against challenge with Mycobacterium tuberculosis.Vaccine27 , 4412–4423 (2009).
   PubMed Web of Science ®Google Scholar
• Manca C , TsenovaL, BergtoldAet al. : Virulence of a Mycobacterium tuberculosis clinical isolate in mice is determined by failure to induce Th1 type immunity and is associated with induction of IFN-α /β.Proc. Natl Acad. Sci. USA98 , 5752–5757 (2001).
   PubMed Web of Science ®Google Scholar
• Jeon BY , DerrickSC, LimJet al. : Mycobacterium bovis BCG immunization induces protective immunity against nine different Mycobacterium tuberculosis strains in mice.Infect. Immun.76 , 5173–5180 (2008).
   PubMed Web of Science ®Google Scholar
• Grode L , SeilerP, BaumannSet al. : Increased vaccine efficacy against tuberculosis of recombinant Mycobacterium bovis bacille Calmette–Guerin mutants that secrete listeriolysin.J. Clin. Invest.115 , 2472–2479 (2005).
   PubMed Web of Science ®Google Scholar
• van der Wel N , HavaD, HoubenDet al. : M. tuberculosis and M. leprae translocate from the phagolysosome to the cytosol in myeloid cells.Cell129 , 1287–1298 (2007).
   PubMed Web of Science ®Google Scholar
• Park JS , TamayoMH, Gonzalez-JuarreroM, OrmeIM, OrdwayDJ: Virulent clinical isolates of Mycobacterium tuberculosis grow rapidly and induce cellular necrosis but minimal apoptosis in murine macrophages.J. Leukoc. Biol.79 , 80–86 (2006).
   PubMed Web of Science ®Google Scholar
• Magalhaes I , SizemoreDR, AhmedRKet al. : rBCG induces strong antigen-specific T cell responses in rhesus macaques in a prime-boost setting with an adenovirus 35 tuberculosis vaccine vector.PLoS ONE3 , E3790 (2008).
   PubMed Web of Science ®Google Scholar
• Madakamutil LT , ChristenU, LenaCJet al. : CD8αα-mediated survival and differentiation of CD8 memory T cell precursors.Science304 , 590–593 (2004).
   PubMed Web of Science ®Google Scholar
• Wang R , NatarajanK, MarguliesDH: Structural basis of the CD8 α β/MHC class I interaction: focused recognition orients CD8 β to a T cell proximal position.J. Immunol.183 , 2554–2564 (2009).
   PubMed Web of Science ®Google Scholar
• Cheroutre H , LambolezF: Doubting the TCR coreceptor function of CD8αα.Immunity28 , 149–159 (2008).
   PubMed Web of Science ®Google Scholar
• Abel B , TamerisM, MansoorNet al. : The novel tuberculosis vaccine, AERAS-402, induces robust and polyfunctional CD4+ and CD8+ T cells in adults.Am. J. Respir. Crit. Care Med.181 , 1407–1417 (2010).
   PubMed Web of Science ®Google Scholar
• Orme IM : The Achilles heel of BCG.Tuberculosis (Edinb.)90(6) , 329–332 (2010).
   PubMed Web of Science ®Google Scholar
• Goldsack L , KirmanJR: Half-truths and selective memory: interferon γ, CD4+ T cells and protective memory against tuberculosis.Tuberculosis (Edinb.)87 , 465–473 (2007).
   PubMed Web of Science ®Google Scholar
• Seder RA , DarrahPA, RoedererM: T-cell quality in memory and protection: implications for vaccine design.Nat. Rev. Immunol.8 , 247–258 (2008).
   PubMed Web of Science ®Google Scholar
• Kagina BM , AbelB, ScribaTJet al. : Specific T cell frequency and cytokine expression profile do not correlate with protection against tuberculosis, following BCG vaccination of newborns.Am. J. Respir. Crit. Care Med.182(8) , 1073–1079 (2010).
   PubMed Web of Science ®Google Scholar
• Lindenstrom T , AggerEM, KorsholmKSet al. : Tuberculosis subunit vaccination provides long-term protective immunity characterized by multifunctional CD4 memory T cells.J. Immunol.182 , 8047–8055 (2009).
   PubMed Web of Science ®Google Scholar
• Kraft SL , DaileyD, KovachMet al. : Magnetic resonance imaging of pulmonary lesions in guinea pigs infected with Mycobacterium tuberculosis.Infect. Immun.72 , 5963–5971 (2004).
   PubMedGoogle Scholar
• Henao-Tamayo MI , OrdwayDJ, IrwinSM, ShangS, ShanleyC, OrmeIM: Phenotypic definition of effector and memory T-lymphocyte subsets in mice chronically infected with Mycobacterium tuberculosis.Clin. Vaccine Immunol.17 , 618–625 (2010).
   PubMedGoogle Scholar
• Palanisamy G , DuTeauN, EisenachKet al. : Clinical strains of Mycobacterium tuberculosis display a wide range of virulence in guinea pigs.Tuberculosis (Edinb.)89 , 203–209 (2009).
   PubMed Web of Science ®Google Scholar
• Palanisamy GS , SmithEE, ShanleyCA, OrdwayDJ, OrmeIM, BasarabaRJ: Disseminated disease severity as a measure of virulence of Mycobacterium tuberculosis in the guinea pig model.Tuberculosis (Edinb.)88 , 295–306 (2008).
   PubMed Web of Science ®Google Scholar
• Green AM , MattilaJT, BigbeeCL, BongersKS, LinPL, FlynnJL: CD4+ regulatory T cells in a cynomolgus macaque model of Mycobacterium tuberculosis infection.J. Infect. Dis.202 , 533–541 (2010).
   PubMed Web of Science ®Google Scholar
• Kremer K , van-der-WerfMJ, AuBKet al. : Vaccine-induced immunity circumvented by typical Mycobacterium tuberculosis Beijing strains.Emerg. Infect. Dis.15 , 335–339 (2009).
   PubMed Web of Science ®Google Scholar
• Cardona PJ , AsensioJG, ArbuesAet al. : Extended safety studies of the attenuated live tuberculosis vaccine SO2 based on phoP mutant.Vaccine27 , 2499–2505 (2009).
   PubMed Web of Science ®Google Scholar
• Comas I , ChakravarttiJ, SmallPMet al. : Human T cell epitopes of Mycobacterium tuberculosis are evolutionarily hyperconserved.Nat. Genet.42 , 498–503 (2010).
   PubMed Web of Science ®Google Scholar
• Mackaness GB : The immunological basis of acquired cellular resistance.J. Exp. Med.120 , 105–120 (1964).
   PubMed Web of Science ®Google Scholar
• Mackaness GB . Resistance to intracellular infection.J. Infect. Dis.123 , 439–445 (1971).
   PubMed Web of Science ®Google Scholar
• Orme IM : Characteristics and specificity of acquired immunologic memory to Mycobacterium tuberculosis infection.J. Immunol.140 , 3589–3593 (1988).
   PubMed Web of Science ®Google Scholar
• Orme IM : Induction of nonspecific acquired resistance and delayed-type hypersensitivity, but not specific acquired resistance in mice inoculated with killed mycobacterial vaccines.Infect. Immun.56 , 3310–3312 (1988).
   PubMed Web of Science ®Google Scholar
• Orme IM , AndersenP, BoomWH: T cell response to Mycobacterium tuberculosis.J. Infect. Dis.167 , 1481–1497 (1993).
   PubMed Web of Science ®Google Scholar